Feasibility Study of Prolonged Administration of Naxitamab, Irinotecan, and Temozolomide for Patients With Relapsed or Refractory Neuroblastoma

NCT07027748 | Recruiting Phase 1 DMC FDA Drug

• 1 other identifier: 25-211
• Study Type: interventional
• Target: 18
• Locations: 1 country
• Sites: 2

Brief Summary

This research is being done to investigate a treatment regimen of Irinotecan, Temozolomide, and Sargramostin, and an immunotherapy called Naxitamab and whether giving Naxitamab more slowly reduces the side effects for participants with relapsed or refractory neuroblastoma. The name of the study drugs involved in this study are:

• Naxitamab (A type of monoclonal antibody)
• Irinotecan (A standard of care chemotherapy)
• Temozolomide (A standard of care chemotherapy)
• Sargramostim (A standard of care, granulocyte-macrophage colony stimulating factor)

Conditions

Neuroblastoma; Neuroblastoma Recurrent; Relapsed Neuroblastoma; Refractory Neuroblastoma

Keywords

Neuroblastoma; Neuroblastoma Recurrent; Relapsed Neuroblastoma; Refractory Neuroblastoma; Progressive Neuroblastoma

Outcome Measures

Primary Outcomes (1)

• Recommended duration of naxitamab infusion

  The duration of naxitamab infusion that is safe and tolerable will be measured using the endpoint of an occurrence of any dose limiting toxicity. A modified 3+3 design will be used, where the 'modification' permits a single duration level de-escalation in addition to the typical duration group level escalation.

  Assessed at the end of the first cycle of treatment, where 1 cycle is 21 days

Secondary Outcomes (9)

• Frequency of severe infusion related pain as measured by NCI Common Terminology Criteria for Adverse Events (CTCAE)

  Assessed days 1 and 8 for Cycles 1 through 6, where 1 cycle is 21 days

• Frequency of severe infusion related pain as measured by the Pediatric Patient-Reported Outcomes version of the Common Terminology Criteria for Adverse Events (PEDS PRO-CTCAE)

  Assessed days 1 and 8 for Cycles 1 through 6, where 1 cycle is 21 days

• Frequency of grade 3 or higher infusion related pain as measured by The Face, Legs, Activity, Cry, and Consolability (FLACC) Scale

  Assessed on every naxitamab infusion day (days 1, 3, and 5) for both Cycle 1 and 2, where 1 cycle is 21 days

• Frequency of grade 3 or higher infusion related pain as measured by the Wong-Baker FACES scale

  Assessed on every naxitamab infusion day (days 1, 3, and 5) for both Cycle 1 and 2, where 1 cycle is 21 days

• Frequency of grade 3 or higher related pain as measured by the Numeric Rating Scale (NRS)

  Assessed on every naxitamab infusion day (days 1, 3, and 5) for both Cycle 1 and 2, where 1 cycle is 21 days

Study Arms (1)

Naxitamab Infusion+ Ironotecan + Temozolomide + Sargramostim

EXPERIMENTAL

Participants will be enrolled in a modified 3+3 design to establish a maximum tolerated, infusion duration for Naxitamab. Dosage will start at Duration Level 1 and will de-escalate to Duration Level -1 or escalate to Duration Level 2 according to dose-limiting toxicity (DLT) criteria. * Baseline visit * Cycle 1 (21 day cycle): * Days 1, 3, and 5: Predetermined dose of Naxitamab 1x daily * Days 1 through 5: Predetermined dose of Temozolomide 1x daily * Days 1 through 5: Predetermined dose of Ironotecan 1x daily * Days 6 through 12: predetermined dose of Sargramostim 1x daily * Cycles 2 through 6 (21 day cycles): * Imaging on Cycles 2, 4, and 6 * Days 1, 3, and 5: Predetermined dose of Naxitamab 1x daily * Days 1 through 5: Predetermined dose of Temozolomide 1x daily * Days 1 through 5: Predetermined dose of Ironotecan 1x daily * Days 6 through 12: predetermined dose of Sargramostim 1x daily * End of treatment visit * Follow up at 1 year post-treatment

Drug: Naxitamab; Drug: Irinotecan; Drug: Temozolomide; Drug: Sargramostim granulocyte-macrophage colony stimulating factor

Interventions

Sargramostim granulocyte-macrophage colony stimulating factor DRUG

Recombinant human granulocyte-macrophage colony stimulating factor (rhu GM-CSF), multi-use vial, via subcutaneously (under the skin) injection per standard of care

Also known as: Leukine

Naxitamab Infusion+ Ironotecan + Temozolomide + Sargramostim

Naxitamab DRUG

Recombinant humanized anti-GD2 monoclonal antibody, single-use vial, via intravenous (into the vein) infusion per protocol.

Naxitamab Infusion+ Ironotecan + Temozolomide + Sargramostim

Irinotecan DRUG

Topoisomerase Inhibitor, single-dose vial, via intravenous infusion per standard of care

Naxitamab Infusion+ Ironotecan + Temozolomide + Sargramostim

Temozolomide DRUG

Alkylating agent, capsule, via orally (by mouth) per standard of care

Also known as: Temodal, Temodar

Naxitamab Infusion+ Ironotecan + Temozolomide + Sargramostim

Eligibility Criteria

• Age: 1 Year - 30 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• Histologic Diagnosis: Patients must have had histologic verification of neuroblastoma or ganglioneuroblastoma or demonstration of neuroblastoma cells in the bone marrow with elevated urinary catecholamines \[i.e. \> 2 x upper limit of normal (ULN)\], at the time of initial diagnosis.
• Relapsed or Refractory Disease Patients must have ONE of the following:
• \) Any prior episode of recurrent high-risk disease following completion of frontline high-risk therapy. Patients may have received other lines of therapy for treatment of recurrent disease prior to enrolling to this trial.
• \) Prior progressive high-risk disease during frontline high-risk therapy. Patients may have received other lines of therapy for treatment of progressive disease prior to enrolling to this trial.
• \) Primary resistant/refractory disease (less than partial response by INRC) detected after the conclusion of at least 4 cycles of aggressive multidrug induction chemotherapy on or according to a high-risk neuroblastoma protocol (examples include ANBL0532, ANBL09P1, ANBL12P1, ANBL1531, ANBL2131) that was treated with additional therapy with the goal of improving remission status prior to enrolling to this trial.
• Documentation of Disease: Patients must have at least ONE of the following at the time of enrollment:
• \) Measurable tumor on MRI or CT scan. Measurable is defined as ≥ 10 mm in at least one dimension (or 15 mm in short axis for lymph node) on spiral/helical CT or MRI that is MIBG avid or demonstrates increased FDG uptake on PET scan.
• \) MIBG-avid lesion detected on MIBG scan with positive uptake at a minimum of one site. This site must represent disease recurrence or known refractory disease at a site not previously radiated.
• \) In patients with known MIBG non-avid disease, FDG-avid lesion detected on FDG- PET scan with positive uptake at a minimum of one site. This site must represent disease recurrence or known refractory disease at a site not previously radiated.
• Of note, patients with isolated bone marrow only disease are NOT eligible for this trial.
• Prior Therapy: Prior lines of anticancer therapy allowed as described in eligibility section above by disease status. Washout periods from prior therapy are as follows:
• Myelosuppressive chemotherapy: Last dose given 14 days prior to enrollment.
• Small molecule targeted therapies (anti-neoplastic agents including retinoids): Last dose given 7 days prior to enrollment.
• Monoclonal antibodies: Last given at least 7 days or 3 half-lives, whichever is longer, prior to enrollment.
• Radiation:

You may not qualify if:

• Chronic (more than 2 weeks duration) diarrhea \> grade 1
• Prior receipt of naxitamab
• Untreated central nervous system (CNS) metastatic disease
• Pregnant or currently breast feeding: Pregnant participants are excluded from this study because protocol therapy has the potential for teratogenic or abortifacient effects. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the parent with protocol therapy, participants planning to continue breastfeeding are excluded from the study.
• Clinically significant arrhythmias, i.e. those that cause clinical symptoms or require medications for control of symptoms
• Prior allergic reaction to irinotecan or temozolomide
• Discontinuation of prior irinotecan or temozolomide due to unacceptable toxicity
• Discontinuation of prior GD2 directed immunotherapy due to unacceptable toxicity other than allergic reaction
• Serious intercurrent illness
• Active uncontrolled infection
• Existing major organ dysfunction CTCAE \>Grade 2, except for hearing loss and hematological status, kidney, and liver function as described in eligibility criteria
• Concomitant Medication Restrictions:
• Patients may not be receiving immunosuppressive medications including pharmacologic doses of glucocorticoids or immunomodulatory agents due to concern for inhibition of antibody effect. Local and inhaled steroid agents are permitted.
• Patients may not be receiving concurrent anti-cancer agents or radiotherapy.
• Patients may not have received valproic acid within 14 days prior to enrollment.

Sponsors & Collaborators

• Steven DuBois, MD: lead
• Y-mAbs Therapeutics: collaborator

Study Sites (2)

Boston Children's Hospital

Boston, Massachusetts, 02115, United States

RECRUITING

Dana-Farber Cancer Institute

Boston, Massachusetts, 02115, United States

RECRUITING

MeSH Terms

Conditions

Neuroblastoma

Interventions

naxitamab; Irinotecan; Temozolomide; sargramostim

Condition Hierarchy (Ancestors)

Neuroectodermal Tumors, Primitive, Peripheral; Neuroectodermal Tumors, Primitive; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue

Intervention Hierarchy (Ancestors)

Camptothecin; Alkaloids; Heterocyclic Compounds; Dacarbazine; Triazenes; Organic Chemicals; Imidazoles; Azoles; Heterocyclic Compounds, 1-Ring

Study Officials

• Steven DuBois, MD, MS

  Dana-Farber Cancer Institute

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Steven DuBois, MD, MS

CONTACT

617-632-5460; Steven_Dubois@dfci.harvard.edu

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Sponsor-Investigator

Model Details: Participants are enrolled sequentially into cohorts corresponding to different naxitamab infusion durations and following a modified 3+3 design for safety assessment.

Study Record Dates

• First Submitted: June 11, 2025
• First Posted: June 18, 2025
• Study Start: June 27, 2025
• Primary Completion (Estimated): December 1, 2026
• Study Completion (Estimated): December 1, 2027
• Last Updated: July 14, 2025

Record last verified: 2025-07

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP
• Time Frame: Data can be shared no earlier than 1 year following the date of publication
• Access Criteria: Contact the Belfer Office for Dana-Farber Innovations (BODFI) at innovation@dfci.harvard.edu

Locations

US (2)